The current proposal is from a group of principal investigators at the University of Colorado Health Sciences Center who have a pressing need for high throughput and automated sequencing and genotyping as a primary research tool. The goal of this proposal is to generate funds to purchase a new Applied Biosystems Genetic Analyzer-DNA Sequencer 3100 to accommodate the increasing demands of the expanding user group at the University of Colorado Health Sciences Center campus. The dominant user group is comprised of faculty members in the existing Diabetes and Endocrinology Research Center (DERC) at the University of Colorado School of Medicine. The user group includes 8 principal investigators at the Barbara Davis Center for Childhood Diabetes, including its Executive Director (G. Eisenbarth) and Research Director (J. Hutton) and additional UCHSC investigators who are DERC members, including the Head of Clinical Immunology (B. Kotzin). At the time of this application, the major users are recipients of over 4 million dollars in yearly NIH support. The instrument requested will alleviate the chronic backlog of sequencing services presently provided to the user group by a single capillary ABI 310 sequencer purchased in 1998 and operated by the newly established DERC molecular core. The instrument requested will be operated and managed using the DERC core facility at the Barbara Davis Center for Childhood Diabetes and its acquisition will permit the user group to more efficiently perform high throughput DNA sequencing. The current instrumentation processes one sample at a time whereas the requested equipment will allow the simultaneous processing of 36 samples per hour. User fees will be charged to fund the management and maintenance of the instrument. Although projected usage should provide enough funding, operating costs not covered by these fees will be absorbed by the Barbara Davis Center with funds provided by the DERC. An advisory group comprised of the DERC molecular core directors (L.Sussel and J. Hutton), two user representatives (one BDC and one non-BDC), and the core manager (S. Hawkes) will provide a balanced management policy for all users.